Abstract
C6 glioma cells were treated with clinically relevant concentrations of valproic acid (0.5 or 1.0 mM) for 1-7 days and RT-PCR used to examine expression of the melatonin MT(1) receptor and selected epigenetic modulators. Valproic acid caused significant time-dependent changes in the mRNA expression of the melatonin MT(1) receptor, histone deacetylase (HDAC) 1, 2 and 3, and methyl CpG binding protein 2 (MeCP2). A structurally distinct HDAC inhibitor, trichostatin A, also caused a significant concentration-dependent induction of melatonin MT(1) receptor mRNA expression, suggesting involvement of an epigenetic mechanism. The ability of clinical concentrations of valproic acid to significantly alter melatonin MT(1) receptor expression, suggests a role for this receptor in the diverse neuropharmacological and oncostatic effects of this agent.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Brain Neoplasms / enzymology
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Brain Neoplasms / genetics*
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Cell Line, Tumor
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Dose-Response Relationship, Drug
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Enzyme Inhibitors / pharmacology
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Epigenesis, Genetic / drug effects
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Gene Expression Regulation, Enzymologic / drug effects*
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Gene Expression Regulation, Neoplastic / drug effects*
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Glioma / enzymology
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Glioma / genetics*
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Histone Deacetylase 1
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Histone Deacetylase 2
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Histone Deacetylase Inhibitors
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Histone Deacetylases / genetics*
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Histone Deacetylases / metabolism
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Hydroxamic Acids / pharmacology
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Methyl-CpG-Binding Protein 2 / genetics*
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Methyl-CpG-Binding Protein 2 / metabolism
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RNA, Messenger / metabolism
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Rats
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Receptor, Melatonin, MT1 / genetics*
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Receptor, Melatonin, MT1 / metabolism
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Repressor Proteins / genetics
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Reverse Transcriptase Polymerase Chain Reaction
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Time Factors
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Valproic Acid / pharmacology*
Substances
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Enzyme Inhibitors
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Histone Deacetylase Inhibitors
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Hydroxamic Acids
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Mecp2 protein, rat
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Methyl-CpG-Binding Protein 2
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RNA, Messenger
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Receptor, Melatonin, MT1
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Repressor Proteins
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trichostatin A
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Valproic Acid
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Hdac1 protein, rat
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Hdac2 protein, rat
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Histone Deacetylase 1
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Histone Deacetylase 2
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Histone Deacetylases
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histone deacetylase 3